The aims of the plan are twofold: to isolate and characterize IgG Fc receptors on human monocytes and macrophages, and to determine the minimum necessary signal for Fc receptor-mediated endocytosis of small immune complexes. The U937 human macrophage cell line will be utilized although for selected experiments, human peripheral blood monocytes and cultured macrophages will be obtained. Receptors will be isolated by three distinct methods: ligand-immobilized affinity chromatography, affinity adsorption using hybridoma anti-Fc receptor antibody, and cross-linking of receptor-ligan complexes with cleavable bifunctional cross-linking reagents followed by purification of the complexes with anti-immunoglobulin reagents. After determining the valence of Fc receptors for IgG, the minimum necessary signal for Fc receptor-mediated endocytosis will be evaluated by determining the fate (dissociation or endocytosis) of small IgG oligomers of specific size made with bivalent cross-linking reagents and by cross-linking Fc receptors using anti-Fc receptor hybridoma antibody. The long term objectives of my laboratory are to develope a model for understanding the molecular events involved in Fc receptors-mediated endocytosis of small immune complexes. An understanding of the cell biology and membrane chemistry of these events will aid in analysis of related immunologic problems in which Fc receptors participate such as antibody-dependent cell-mediated killing of tumor cells, secretion of effector molecules from phagocytic cells, and immunoregulation by lymphocytes.